Presence of angiotensin II in the brain and its centrally mediated hypertensive action is well recognized. However, the pathway, sites and control mechanism of the formation of angiotensin II are not understood. This is because we have not known whether true renin exists in the brain or the renin-like activity is due to cathepsin. We have developed new methodologies to distinguish true brain renin from the non-specific renin-like activity of cathepsin. Specific antibodies against renin are now available for histochemical identification and localization of brain renin. With the ultimate objective of determining the mechanism of angiotensin II formation in the brain, we propose to elucidate the intracerebral role of renin by determining the regional localization of renin in the brain in relation to the localization of angiotensin II by biochemical, anatomical, immunohistochemical, neuropharmacological and cell biological approach. Poosible intraneuronal and intracellular localization of renin will be examined and its release mechanism will be determined. Role and interplay of central renin-angiotensin and catecholamines will be studied in relation to hypertension using spontaneously hypertensive rats as the model of an essential hypertension. Basic information obtained on the regional localization of renin and its relationship to the localization of angiotensin II and to the specific neuronal function are expected to reveal mechanisms by which the brain renin angiotensin system functions and is regulated. These studies will rectify the serious confusion caused by mistaking the renin-like activity of brain cathepsins as renin. Methodologies and concepts developed in these studies will also contribute to our understanding of the mechanism of the formation of many other peptide hormones found in neuronal cells.